Endothelin is an endogenous bioactive peptide composed of 21 amino acids, and three types of which, i.e., endothelin-1, endothelin-2, and endothelin-3 are known.
Endothelin is a bioactive substance for continuously constricting vascular or non-vascular smooth muscle in direct or indirect way (regulation of release of a variety of endogenous substances), and production of endothelin increases due to lesion of endothelium. Excessive production of endothelin is considered to be a cause for diseases such as hypertension, pulmonary hypertension, Buerger disease, primary Raynaud syndrome, asthma, eyegrounds (amphiblestrodes, chorioidea, and the like) diseases, diabetes, arterial sclerosis, renal failure, cardiac infarction, angina pectoris, cerebrovascular contraction, and cerebral infarction. Furthermore, it is known that endothelin is an important mediator with respect to multiple organ failures, and diseases such as disseminated intravascular coagulation due to endotoxin shock and the like as well as renal lesion induced by cyclosporin and the like. Moreover, it is also known that an endothelin concentration in blood increases after organ transplantation such as liver transplant.
Prostanoic acid is a skeletal compound constituting a common structural feature of natural prostaglandins (PG) groups and is represented by the following structural formula: ##STR1##
Natural PG groups are classified based on the structural feature of five-membered ring into PGA group, PGB group, PGC group, PGD group, PGE group, PGF group, PGG group, PGH group, PGI group, and PGJ group; and further they are classified as follows on the basis of presence or absence of unsaturation and oxidation at their chain portions:
numerical subscript 1 . . . 13,14-unsaturated-15-OH PA0 numerical subscript 2 . . . 5,6- and 13,14-di-unsaturated-15-OH PA0 numerical subscript 3 . . . 5,6,13,14- and 17,18-tri-unsaturated-15-OH
Moreover, the PGF group is classified into .alpha. (hydroxy group is in alpha-configuration) and .beta. (hydroxy group is in beta-configuration) based on the configuration of hydroxy group at 9-position. In addition, a compound having oxo group in place of hydroxy group at 15-position is also known.
With respect to action of prostanoic acid compound on endothelin, it has been reported, for example, that PGE.sub.2 inhibits renal endothelin inducible vasoconstriction in rat, and that prostacyclin (PGI.sub.2) moderates renal endothelin inducible vasoconstriction in dog.
However, any of these prostanoic acid compounds is the one wherein the basic carbon atoms in .alpha.-chain are 7, and hence, they do not correspond to the prostanoic acid compound wherein the skeletal carbon atoms in a-chain increase.
U.S. Pat. No. 3,974,195 and European Patent Application Laid-Open No. 0453127 (corresponding to Japanese Patent Kokai Hei 5-58992) describe a compound wherein the skeletal carbon atoms in .alpha.-chain are increased by 2, but there is no description as to the action with respect to endothelin in these both publications.